Medicine Matters Diabetes

Potential roles of autoreactive B cells in diabetic kidney disease

Autoreactive B cells in the blood and peripheral lymphoid organs can lose anergy and become activated through a variety of potential mechanisms. Collaboration with CD4+ helper T cells leads to the proliferation and differentiation of B cells that secrete inflammatory cytokines and the development of plasma cells that secrete autoantibodies, which can form immune complexes. The localization of this response is not yet fully understood; however, we hypothesize that these immune complexes, together with complement, can infiltrate the glomeruli, leading to mesangial expansion and thickening of the glomerular basement membrane. The presence of immune complexes in the glomerulus also induces macrophage accrual, promoting inflammation. The release of damage-associated molecular patterns following damage to the extracellular matrix, can lead to further B cell activation, leading to further cytokine production.